OMF Volunteer Correspondent

On this #OMFScienceWednesday we are pleased to introduce you to a central member of the OMF-funded ME/CFS Collaborative Research Center team at the Stanford Genome Technology Center (SGTC), Mohsen Nemat-Gorgani, PhD. Dr. Nemat-Gorgani is leading a team to investigate the Red Blood Cells (RBC) in ME/CFS patients. Mohsen shared his story with OMF.

"I was born and raised in Iran, and did my undergraduate and graduate studies in U.K. In 1974, I obtained a PhD in biochemistry from Warwick University, and after a year of postdoctoral training at Vanderbilt, I returned to Iran. In October 2003, I came to the Stanford Genome Technology Center (SGTC) as a Visiting Professor from Tehran University, and continued working as a Research Associate upon termination of the sabbatical leave. During my time at the Center, I participated in various technology development projects, and about two years ago, after a brief absence from the Center, I started working on ME/CFS.

Upon participation in the ME/CFS project, and during the first few months of my presence at the Center, I learnt, mainly by talking to Ron Davis, Laurel Crosby and a number of patients, that inadequate blood flow to tissues could be the cause of some of the symptoms reported in ME/CFS. It also became known to me that red blood cells (RBCs) and their mechanical properties may largely determine the rheological (deformation and flow) behavior of blood in normal and disease states.

Interestingly, a few years before working on ME/CFS, I was somewhat involved in a study on the mechanical properties of breast cancer cells at the Center. This work was conducted by Shane Crippen, a graduate student under the guidance of Ron Davis, Roger Howe and Stefanie Jeffrey (Electrical Engineering and Stanford Medical School, respectively). In the course of subsequent discussions (in June 2016) with Ron and Roger, it was decided that we should look at the mechanical properties of RBCs related to ME/CFS, and we started exploring different technical approaches to achieve this goal.

In January 2017, during a visit to SJSU, I met Anand Ramasubramanian who had recently taken up a faculty position in the Chemical and Materials Engineering Department. Anand had previously looked at deformability of monocytes using a microfluidic platform, and during the course of our discussions, it became obvious that a collaboration with his team (involving Amit Saha, who had worked with Anand on monocyte deformability as a part of his Ph.D. thesis, and graduate students) would be an effective way of going forward. Few months later, the studies were initiated, and with the outstanding technical support provided by Julie Wilhelmy and Layla Cervantes, samples from a large number (over 30) of CFS patients and healthy controls were collected at the SGTC, and later analyzed at SJSU.

RBC deformability is believed to play an important role in their main function - the transport of oxygen and carbon dioxide via blood circulation. They are highly elastic, which allows them to flow easily. The reason for this exceptional property is found in the composition of the membrane and the membrane-cytoskeleton interaction. A healthy RBC is approximately 8.0 µm in diameter, which needs to undergo large deformations in order to pass through capillaries, around 2-3 µm in diameter. A slight decrease in deformability has been shown to cause a significant increase in microvascular flow resistance, with important physiological implications.

RBC deformability has been shown to be impaired in various pathologies including inflammatory conditions such as sepsis. Recent studies have clearly indicated that inflammation is involved in ME/CFS. Moreover, RBCs are highly susceptible to oxidative stress due to the high contents of polyunsaturated fatty acids in the cell membrane, a process that may impair deformability, and some studies have indicated RBC oxidative damage occurring in ME/CFS.

Using the microfluid platform, the mechanical properties of RBCs from CFS and healthy control samples have been compared by determination of the time taken to enter the channels as well as transit velocity, and elongation capacity. Our preliminary results suggest clear differences in deformability of RBCs from CFS and healthy control blood samples using this platform. A manuscript has recently been submitted for publication describing these observations.

The zeta potential and related studies are expected to be in collaboration with Gerald Fuller’s group (Professor, Chemical Engineering, Stanford).

Financial support for all these efforts has been provided by OMF. It is hoped that differences in RBC mechanical properties will serve as a label-free biomarker in CFS diagnosis. We hope the described collaborative efforts will help us develop a diagnostic device for ME/CFS.

It is a great pleasure and privilege to be part of Ron’s team, and to try to contribute toward solving the mystery of ME/CFS."

Thank you Mohsen for providing us with a detailed look into the potential effects of RBC alterations and for leading a stellar team. We sincerely appreciate your work with Dr. Davis.

I’m very glad to read there’s a publication in the pipeline. This research sounds very interesting.

I’m also very impressed by the amount of brilliant researchers that have entered the field in the past couple of years. That by itself is a miracle in this systematically neglected disease.
I’m extremely grateful for that!

Senior Member

Sometimes I wonder if part of the benefit people anecdotally are getting from HBOT and Ozone is due to increased peripheral tissue oxygenation. Not to start a discussion on alternative medicine right here taking anecdotes as true information, but anyway it seems like there are a lot of people from a lot of chronic diseases reporting some benefits. And most of these disease states show some form of rheological dysfunction.

Senior Member

I can't remember the name of the researcher in NZ who found that blood cells in ME patients were deformed and couldn't get into small blood vessels. His research was "disproved" by other groups who could not replicate his findings.

He told them over and over that he looked at fresh blood because if you put the cells into transport medium they regained their shape. Typically in the sad story of ME research no one paid attention and another promising avenue was neglected and died.

It infuriates me that over the years there have been interesting findings which have never been investigated properly.

Senior Member

I can't remember the name of the researcher in NZ who found that blood cells in ME patients were deformed and couldn't get into small blood vessels. His research was "disproved" by other groups who could not replicate his findings.

He told them over and over that he looked at fresh blood because if you put the cells into transport medium they regained their shape. Typically in the sad story of ME research no one paid attention and another promising avenue was neglected and died.

It infuriates me that over the years there have been interesting findings which have never been investigated properly.

We met with him two decades ago on one of his trips to the US to discuss a potential collaboration with Dr. Shu Chien, University of California, San Diego, to develop a "bioengineering model" of the RBC abnormalities he had observed in ME/CFS.

He would be very pleased with the work Ron Davis and his team are doing, I believe, all these years later.@Janet Dafoe (Rose49)

I wonder if we could do some science here. Collecting samples from multiple patients would be hard but imagine if we could even trace changes in RBC presentation in one patient between a crash and a period of feeling relatively well.

Senior Member

Nondiscocytic erythrocytes in myalgic encephalomyelitis.Simpson LO1.
Department of Pathology, University of Otago Medical School, Dunedin.Abstract
Blood samples from 102 volunteers who believed they suffered from myalgic encephalomyelitis were photographed in a scanning electron microscope at 500x. All identifiable cells were counted and classified on the basis of their shape. The frequency of each cell shape was expressed as a percentage of the total number of cells counted in the sample.

The resulting data were compared with that from 52 healthy controls and 99 cases of multiple sclerosis which had been selected randomly by a computer from a panel of 229 cases in a concurrent study.

Samples from subjects with myalgic encephalomyelitis had the lowest percentages of normal red cells and the highest incidence of cup forms. The results provide evidence that myalgic encephalomyelitis has an organic cause. Quantitative analysis of red cell shape may assist in the diagnosis of myalgic encephalomyelitis.

@Murph, interestingly Simpson did a self-experiment sampling his blood every day after an infection that had caused his RBCs to become misshapen. He reported it took 14 days post-infection for them to return to a normal shape.

He also observed that patient's who respond to slight or moderate stress or "exertion" by becoming physically and/or mentally exhausted had increased numbers of misshapen RBCs. Perhaps Maureen Hansen and others will consider RBCs and circulation in their PEM research....

Senior Member

Some technology like Seahorse for metabolic profiling didn't exist until recently, but to find out that we could have had objective biomarker for ME 30 freaking years ago simply by looking at red blood cells is just....

What paychiatry's grip on this illness has done to generations of patients makes me feel like it borders on crimes against humanity.

I react badly to blood thinners. Some were improved by heparin, many were not, according to what I recollect. Heparin will help with coagulation issues, I am not sure it helps with red blood cell deformability.

Increasing short chain polyunsaturated fatty acids might help, both omega 6s and omega 3s, but there are risks with that too. In 1993 I was part of an investigation into these fats and ME. Some patients respond. I may have been the first to try high dose omega 3s from plants in such a setting. While some papers were published they were all either hypotheses or pilot studies.

These fats not only increase cell flexibility, they are the basis for synthesis of a class of hormones called eicosanoids. Its because of this that direct supplementation may have risks, as it will alter hormone synthesis balance. Saturated fat decreases RBC deformability. I am less clear about omega 9 fats, they might be good and are hormone neutral but I have never seen good data on this.

Lowering oxidative stress might help also, with a good variety of antioxidants including C, E, lipoic, and CoQ10, and natural plant antioxidants. NAC might also help. These can help protect the lipid layers on cells. Vitamin E, glutathione and CoQ10 are likely to be deficient in us.

However there is no substitute for figuring out what is going on and clinical trials.

We should have had these studies decades back. Its good this is happening now, and its much better with advances in technology, but it is right this is one more overlooked issue. There are so many in ME.